chr1-235379947-C-CAA

Variant names:

• chr1-235379947-C-CAA
• rs36068852
• NM_003193.5:c.-31-56_-31-55dupAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003193.5(TBCE):​c.-31-56_-31-55dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 721,796 control chromosomes in the GnomAD database, including 48 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (47 hom., cov: 0)
  • Exomes 𝑓: 0.060 (1 hom.)
• Consequence: TBCE NM_003193.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

Genes affected

TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000285053 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCE	NM_003193.5	c.-31-56_-31-55dupAA		intron_variant	Intron 1 of 16	ENST00000642610.2	NP_003184.1
TBCE	NM_001287801.2	c.-31-56_-31-55dupAA		intron_variant	Intron 1 of 17		NP_001274730.1
TBCE	NM_001079515.3	c.-31-56_-31-55dupAA		intron_variant	Intron 1 of 16		NP_001072983.1
TBCE	NM_001287802.2	c.-341-56_-341-55dupAA		intron_variant	Intron 1 of 15		NP_001274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCE	ENST00000642610.2	c.-31-72_-31-71insAA		intron_variant	Intron 1 of 16		NM_003193.5	ENSP00000494796.1
ENSG00000285053	ENST00000645655.1	c.-31-72_-31-71insAA		intron_variant	Intron 4 of 19			ENSP00000495202.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2092 AN: 132670 Hom.: 47 Cov.: 0

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.00714

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.000914

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.00451

Gnomad FIN AF: 0.00477

Gnomad MID AF: 0.0141

Gnomad NFE AF: 0.00222

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0600 AC: 35367 AN: 589096 Hom.: 1 AF XY: 0.0586 AC XY: 18149 AN XY: 309518

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.0435

Gnomad4 ASJ exome AF: 0.0657

Gnomad4 EAS exome AF: 0.0731

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0622

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0158 AC: 2101 AN: 132700 Hom.: 47 Cov.: 0 AF XY: 0.0157 AC XY: 988 AN XY: 63066

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.00714

Gnomad4 ASJ AF: 0.000914

Gnomad4 EAS AF: 0.0345

Gnomad4 SAS AF: 0.00452

Gnomad4 FIN AF: 0.00477

Gnomad4 NFE AF: 0.00222

Gnomad4 OTH AF: 0.0138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36068852; hg19: chr1-235543262;